Preeclampsia, eclampsia and pregnancy induced hypertension (PIH) are characterized by elevated blood pressure, proteinuria, and edema. The cause and nature of these disorders is only partially understood. Preeclampsia and PIH are often used to designate the same disorders. The term "preeclampsia" is used hereinafter, for purposes of clarity of explanation, not by way of limitation, to broadly include preeclampsia, pregnancy induced hypertension, and eclampsia. Although considered to be relatively rare in the United States, preeclampsia occurs worldwide in from 2 to 35 percent of pregnancies, depending on diagnostic criteria and study population. Deaths from preeclampsia are nearly equal to those from eclampsia in a recent report by Redman, C. Brit.Med.J. 296:1209-1210 (April, 1988). However, tests for these conditions are often ambiguous, and diagnosis of these conditions have often not been possible until the condition had progressed. A reliable test for early diagnosis of this condition is critically needed.
A review of the role of prostaglandins in preeclampsia was published by Friedman, S. Obstet.Gynecol.71:122-137 (1988). Examination of maternal fluids for metabolic markers for PIH and preeclampsia has revealed that urine levels of 2,3-dinor-6-keto PG F.sub.1.alpha. increase during this condition, Ob/Gyn Topics, 2:5 (1987). Levels of other substances in the blood have also been studied.
A number of studies have focused on the general increase in fibronectin levels in blood during these disease processes: Graninger, W. et al, Europ.J.Obstet.Gynec.Reprod.Biol., 19:223-229 (1985); Hess, L, et al Obstret.Gynecol. 68:25-28 (1986); Lazarchick, J. et al, Am.J.Ob.Gyn. 154:1050-1052 (1986); Ericksen, H. et al, Acta.Obstet.Gynecol.Scand. 66:25-28 (1987); and Saleh, A. et al, Obstet.Gynecol. 71:719 (1988), for example. Although fibronectin levels in the blood were reportedly higher with PIH and preeclampsia, the degree of increase varied with each individual and stage of pregnancy, and considered alone, was not a reliable diagnostic indicator of the disease. Sibai, B. et al, Contemp.Ob/Gyn. 57 (Feb. 1988) reports that the search continues for a reliable means for forecasting PIH and effective ways to reduce incidence. In the meantime, clinicians still continue using blood pressure criteria to guide management.
That the elevated fibronectin level observed with preeclampsia suggested endothelial injury was postulated by Bhatia, R. et al, Am.J.Obstet.Gynecol. 157:106-108 (1987). More recently, Roberts (Ob.Gyn.News. 221 (Nov. 1987) has suggested that the evidence suggests that preeclampsia is a disease process fundamentally related to endothelial cell injury, not a hypertensive disorder.
Monoclonal antibodies which bind preferentially with human cellular fibronectin and can distinguish between the cellular fibronectin and plasma fibronectin are described by Keen, J. et al, Mol.Biol.Med. 2:15-27 (1984). Monoclonal antibodies which bind with a unique Ed sequence of cellular fibronectin in embryonic and adult human tissues are described by Vartio, T. et al, J.CellSci. 88:419-430 (1987). Unique amino acid stretches present in human fibronectin are reported by Gutman, A. et al, Proc.Na;tl.Acad.Sci.USA. 84:7179-7182 (1987). Peters, J. et al, Am.Rev.Respir.Dis. 138:167-174 (1988) describes the synthesis of an Extra Type III Domain (ED1) peptide corresponding to a unique nonhomologous stretch of 29 amino acids present in human cellular fibronectin, antibodies binding with this region, and an ELISA immunoassay developed with these antibodies. The peptide sequence disclosed is TYSSPEDGIHELFPAPDGEEDTAELQGGC, using the single letter abbreviations for alanine (A), cysteine (C), aspartic acid (D), glutamic acid (E), phenylalanine (F), glycine (G), histidine (H), isoleucine (I), leucine (L), proline (P), glutamine (Q), serine (S), threonine (T), and tyrosine (Y).